Striatal D2 and D3 dopamine receptors are involved in mediating the reinforcing
properties of natural rewards and drugs. In Parkinson’s disease, while D2/3
dopamine agonists alleviate motor symptoms, behavioral addictions and withdrawal
syndrome are reported in up to 15% of patients. The origin of such adverse
effects is poorly understood but suggests that D2/3 agonists could possess
reinforcing properties. We evaluated the reinforcing properties of the widely
used D2/3 agonist, Pramipexole (PPX), in normal and parkinsonian rats.
Intracerebroventricular injections of 6-OHDA induced a bilateral loss of tyrosine
hydroxylase-positive cells in the substantia nigra (-51%) and ventral tegmental
area (-31%). The animals were then allowed to self-administer intravenous PPX
under fixed ratio and progressive ratio (PR) reinforcement schedules before being
tested for extinction of PPX seeking. While parkinsonian were slower than sham
rats in acquiring self-administration behavior, they later reached the same level
of intake. The reinforcing value of PPX, as assessed during PR and extinction,
was moderate in both groups. PPX heightened ∆FosB expression in dorsal striatum
of lesioned rats and similar PR results involved different striatal subregions
between groups. Altogether, our results show that drug-naïve rats self-administer
PPX and that the dopaminergic lesion does not affect its reinforcing effects.
While PPX reinforcing value was moderate in most rats, a subset of animals
displayed a high number of responses and appeared to be particularly sensitive to
this drug. These data suggest that PPX may not be responsible for the reported
side-effects but rather call for further investigating the differential
vulnerability among individuals.